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Identification of uniquely expressed transcription factors in highly purified B-cell lymphoma samples†‡§
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U.A. contributed to the design of the study, was responsible for the analysis of the microarray data, performed statistical analysis and wrote the manuscript; P.E. contributed to the design of the study and final decision on statistical analysis of gene expression data and revision of the manuscript; C.P. contributed to the design of the study, discussions on statistical analysis of gene expression data and revision of the manuscript; C.M.H. responsible for preparation and flow cytometry sorting of non-malignant B-cells and revision of the manuscript; M.J. contributed to the design of the study and the revision of the manuscript; N.A. responsible for evaluation of material and clinical data for material (L-MCL) used for gene expression analysis; M.B. provided clinical data, identified and collected samples used for gene expression analysis and revision of the manuscript; C.S. responsible for diagnosis and selection of material used for gene expression analysis; R.R. responsible for collection of samples used for gene expression analysis and revision of the manuscript; C.A.K.B. contributed to the design of the study and revision of the manuscript; S.E. Responsible for the design of the study, interpretation of data and writing of the manuscript.
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All authors approved of the final manuscript.
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Conflicts of Interest: Nothing to report
Abstract
Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc.